Cell proliferation and STAT6 pathways are negatively regulated in T cells by STAT1 and suppressors of cytokine signaling

Suppressor of cytokine signaling (SOCS) proteins have emerged as important regulators of cytokine signals in lymphocytes. In this study, we have investigated regulation of SOCS expression and their role in Th cell growth and differentiation. We show that SOCS genes are constitutively expressed in naive Th cells, albeit at low levels, and are differentially induced by Ag and Th-polarizing cytokines. Whereas cytokines up-regulate expression of SOCS1, SOCS2, SOCS3, and cytokine-induced Src homology 2 protein, Ags induce down-regulation of SOCS3 within 48 h of Th cell activation and concomitantly up-regulate SOCS1, SOCS2, and cytokine-induced Src homology 2 protein expression. We further show that STAT1 signals play major roles in inducing SOCS expression in Th cells and that induction of SOCS expression by IL-4, IL-12, or IFN-gamma is compromised in STAT1-deficient primary Th cells. Surprisingly, IL-4 is a potent inducer of STAT1 activation in Th2 but not Th1 cells, and SOCS1 or SOCS3 expression is dramatically reduced in STAT1(-/-) Th2 cells. To our knowledge, this is the first report of IL-4-induced STAT1 activation in Th cells, and suggests that its induction of SOCS, may in part, regulate IL-4 functions in Th2 cells. In fact, overexpression of SOCS1 in Th2 cells represses STAT6 activation and profoundly inhibits IL-4-induced proliferation, while depletion of SOCS1 by an anti-sense SOCS1 cDNA construct enhances cell proliferation and induces constitutive activation of STAT6 in Th2 cells. These results are consistent with a model where IL-4 has dual effects on differentiating T cells: it simulates proliferation/differentiation through STAT6 and autoregulates its effects on Th2 growth and effector functions via STAT1-dependent up-regulation of SOCS proteins.     

Micro-assembly of functionalized particulate monolayer on C18-derivatized SiO2 surfaces

This work describes a simple approach to immobilize functionalized colloidal microstructures onto a C(18)-coated SiO(2) substrate via specific or non-specific bio-mediated interactions. Biotinylated bovine serum albumin pre-adsorbed onto a C(18) surface was used to mediate the surface assembly of streptavidin-coated microbeads (2.8 microm), while a bare C(18) surface was used to immobilize anti-Listeria antibody-coated microbeads (2.8 microm) through hydrophobic interactions. For a C(18) surface pre-adsorbed with bovine serum albumin, hydrophobic polystyrene microbeads (0.8 microm) and positively charged dimethylamino microbeads (0.8 microm) were allowed to self-assemble onto the surface. A monolayer with high surface coverage was observed for both polystyrene and dimethylamino microbeads. The adsorption characteristics of Escherichia coli and Listeria monocytogenes on these microbead-based surfaces were studied using fluorescence microscopy. Both streptavidin microbeads pre-adsorbed with biotinylated anti-Listeria antibody and anti-Listeria antibody-coated microbeads showed specific capture of L. monocytogenes, while polystyrene and dimethylamino microbeads captured both E. coli and L. monocytogenes non-specifically. The preparation of microbead-based surfaces for the construction of microfluidic devices for separation, detection, or analysis of specific biological species is discussed.     

Effect of obesity on high-density lipoprotein metabolism

Reduced levels of high-density lipoproteins (HDL) in non-obese and obese states are associated with increased risk for the development of coronary artery disease. Therefore, it is imperative to determine the mechanisms responsible for reduced HDL in obese states and, conversely, to examine therapies aimed at increasing HDL levels in these individuals. This paper examines the multiple causes for reduced HDL in obese states and the effect of exercise and diet--two non-pharmacologic therapies--on HDL metabolism in humans. In general, the concentration of HDL-cholesterol is adversely altered in obesity, with HDL-cholesterol levels associated with both the degree and distribution of obesity. More specifically, intra-abdominal visceral fat deposition is an important negative correlate of HDL-cholesterol. The specific subfractions of HDL that are altered in obese states include the HDL2, apolipoprotein A-I, and pre-beta1 subfractions. Decreased HDL levels in obesity have been attributed to both an enhancement in the uptake of HDL2 by adipocytes and an increase in the catabolism of apolipoprotein A-I on HDL particles. In addition, there is a decrease in the conversion of the pre-beta1 subfraction, the initial acceptor of cholesterol from peripheral cells, to pre-beta2 particles. Conversely, as a means of reversing the decrease in HDL levels in obesity, sustained weight loss is an effective method. More specifically, weight loss achieved through exercise is more effective at raising HDL levels than dieting. Exercise mediates positive effects on HDL levels at least partly through changes in enzymes of HDL metabolism. Increased lipid transfer to HDL by lipoprotein lipase and reduced HDL clearance by hepatic triglyceride lipase as a result of endurance training are two important mechanisms for increases in HDL observed from exercise.     

The Potential Efficacy of Glycyrrhizic Acid and Its Nanostructure Against Brown Rot of Peach fruits

Production of peaches (Prunus persica (L.) Batsch) for both local market and export is increasing each year in Egypt. Brown rot disease, caused by Monilinia laxa and Monilinia fructigena, is considered one of the most important postharvest rots affecting peaches in Egypt and economic losses are increasing. Antifungal activity of glycyrrhizic acid nanoparticles (GA-NPs) and glycyrrhizic acid (GA) at 0.2 and 0.4 mmol/L was investigated as a control for both these brown rot pathogens on peach fruits in both in vitro and in vivo studies. In the in vitro studies, GA-NPs were the most effective as shown by the ability to decrease linear growth of both brown rot pathogens in potato dextrose agar (PDA) amended with 0.4 mmol/L GA-NPs. Micrographs of M. fructigena exposed to 0.4 mmol/LGA showed mycelial deformations, nodule formation, detachment of the cell wall, shrinkage and inhomogeneous cytoplasmic materials with large vacuoles. Mycelium of M. laxa exposed to 0.4 mmol/ LGA-NPs resulted in thinner and distorted hyphae, nodule formation, cell wall thinning, and swellings. The GANPs and GA treatments improved fruit quality by maintaining firmness and total soluble solids (TSS). GA-NPs were more effective in decreasing decay incidence than their bulk material. The 0.4 mmol/L GA-NPs completely inhibited the disease on naturally infected peach fruits for both seasons of 2018 and 2019. Furthermore, 0.4 mmol/L GA-NPs reduced the disease incidence in inoculated fruits by 95 (M. laxa) and 88% (M. fructigena) in 2018 season and 96 (M. laxa) and 85% (M. fructigena) in 2019 season. In conclusion, GA-NPs could enhance the resistance of peaches against brown rot caused by M. laxa and M. fructigena.     

FMiR: A Curated Resource of Mitochondrial DNA Information for Fish

Mitochondrial genome sequences have been widely used for evolutionary and phylogenetic studies. Among vertebrates, fish are an important, diverse group, and their mitogenome sequences are growing rapidly in public repositories. To facilitate mitochondrial genome analysis and to explore the valuable genetic information, we developed the Fish Mitogenome Resource (FMiR) database to provide a workbench for mitogenome annotation, species identification and microsatellite marker mining. The microsatellites are also known as simple sequence repeats (SSRs) and used as molecular markers in studies on population genetics, gene duplication and marker assisted selection. Here, easy-to-use tools have been implemented for mining SSRs and for designing primers to identify species/habitat specific markers. In addition, FMiR can analyze complete or partial mitochondrial genome sequence to identify species and to deduce relational distances among sequences across species. The database presently contains curated mitochondrial genomes from 1302 fish species belonging to 297 families and 47 orders reported from saltwater and freshwater ecosystems. In addition, the database covers information on fish species such as conservation status, ecosystem, family, distribution and occurrence downloaded from the FishBase and IUCN Red List databases. Those fish information have been used to browse mitogenome information for the species belonging to a particular category. The database is scalable in terms of content and inclusion of other analytical modules. The FMiR is running under Linux operating platform on high performance server accessible at URL http://mail.nbfgr.res.in/fmir.     

Mechanisms that promote bacterial fitness in fungal-affected soil microhabitats

Soil represents a very heterogeneous environment for its microbiota. Among the soil inhabitants, bacteria and fungi are important organisms as they are involved in key biogeochemical cycling processes. A main energy source driving the system is formed by plants through the provision of plant-fixed (reduced) carbon to the soil, whereas soil nitrogen and phosphorus may move from the soil back to the plant. The carbonaceous compounds released form the key energy and nutrient sources for the soil microbiota. In the grossly carbon-limited soil, the emergence of plant roots and the formation of their associated mycorrhizae thus create nutritional hot spots for soil-dwelling bacteria. As there is natural (fitness) selection on bacteria in the soil, those bacteria that are best able to benefit from the hot spots have probably been selected. The purpose of this review is to examine the interactions of bacteria with soil fungi in these hot spots and to highlight the key mechanisms involved in the selection of fungal-responsive bacteria. Salient bacterial mechanisms that are involved in these interactions have emerged from this examination. Thus, the efficient acquisition for specific released nutrients, the presence of type-III secretion systems and the capacity of flagellar movement and to form a biofilm are pinpointed as key aspects of bacterial life in the mycosphere. The possible involvement of functions present on plasmid-borne genes is also interrogated.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.